This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This study will utilize baboons. We will create a deficiency in insulin secretion by removing part of the pancreas, a procedure called a partial pancreatectomy. We intend to prove that the amount of insulin released is decreased after such pancreatic surgery, and that specific pharmacological treatments might preserve insulin production and release, even in the presence of b-cell stress (the cells responsible for insulin production) resulting from such surgery. The drug to be tested is called exenatide, a medication approved as an antidiabetic pharmacotherapy in humans. In order to precisely measure the amount of insulin secreted, we will create an acute increase in insulin secretory demand by a procedure called a hyperglycemic clamp, where we administer a large amount of glucose intravenously in order to maintain a fixed glucose concentration in the bloodstream of the baboons while measuring the corresponding response in insulin production. We expect to observe changes in insulin levels before and after the partial pancreatectomy. We also hope to demonstrate that exenatide improves B-cell function after partial pancreatectomy. This type of research is extremely valuable for helping to develop potential new treatments for type 2 diabetes.